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Severe course of Lyme neuroborreliosis in an HIV-1 positive patient; case report and review of the literature
© van Burgel et al; licensee BioMed Central Ltd. 2010
Received: 16 June 2010
Accepted: 30 November 2010
Published: 30 November 2010
Lyme Neuroborreliosis (LNB) in a human immunodeficiency virus (HIV) positive patient is a rare co-infection and has only been reported four times in literature. No case of an HIV patient with a meningoencephalitis due to LNB in combination with HIV has been described to date.
A 51 year old woman previously diagnosed with HIV presented with an atypical and severe LNB. Diagnosis was made evident by several microbiological techniques. Biochemical and microbiological recovery during treatment was rapid, however after treatment the patient suffered from severe and persistent sequelae.
A clinician should consider LNB when being confronted with an HIV patient with focal encephalitis, without any history of Lyme disease or tick bites, in an endemic area. Rapid diagnosis and treatment is necessary in order to minimize severe sequelae.
Lyme Neuroborreliosis (LNB) in a human immunodeficiency virus (HIV) positive patient is a rare co-infection and has only been reported four times [1–4]. All published cases are early presentations of Lyme disease and no report of a meningoencephalitis due to B. burgdorferi in an HIV patient has been made to date. We present a case of an HIV positive patient that presented with a severe LNB, without any previous sign of Lyme disease.
A 51-year-old woman, diagnosed with HIV 10 years before, presented early spring 2006 at the outpatient clinic in the west of the Netherlands. She had noticed an altered gait that was progressive since three months. Strength and sensibility were unaltered, but there was paresthesia in both legs. She also had problems unbuttoning clothing with both hands. There was no complaint of headache, photophobia or visual changes. The medical history showed an anxiety disorder, hypertension and glaucoma. At presentation, the patient had been using HAART for six years (zidovudine, lamivudine and nevirapine) in combination with antihypertensive medication and a selective serotonin reuptake inhibitor. There was no indication for antibiotic prophylaxis. She had no history of tick bites, rash, erythema migrans or other signs of early or late-stage Lyme borreliosis. However, she frequently worked in her garden in an area where B. burgdorferi is endemic. Neurological examination revealed a bipyramidal walking pattern, an intention tremor of the posture and the hands, bilateral hyperreflexia in her legs and arms, a positive Hoffman-Trömner and a bilateral Babinski. There were no meningeal signs and all cranial nerve function was intact. RR was 190/113 and temperature was normal. Routine laboratory tests showed no signs of infection; blood leucocytes level was 5,9*109/l. Plasma HIV RNA load was undetectable, CD4+ T lymphocyte count was 501/μl. A lumbar puncture was performed; the opening pressure was 28 cm H2O. The cerebrospinal fluid (CSF) showed a leucocytosis of 201/μl, 70% T-lymphocytes, 6% NK-cells, and 6% B-lymphocytes, glucose 2 mmol/l (serum glucose 6,2 mmol/l), protein 1,26 g/L. By isoelectric focussing oligoclonal IgG was detected intrathecally, but there was no evidence of a monoclonal B-cell population. Cytology and immunophenotyping of the intrathecal leucocytes were negative for haematological malignancies.
CSF was examined and found PCR negative for HIV RNA, neurotropic viruses (Cytomegalovirus, Epstein Barr, Varicella zoster virus, Herpes simplex virus, JC virus), tuberculosis, toxoplasmosis, Bartonella and Treponema pallidum. CSF and serum serology was negative for T. pallidum and cryptococcal antigens. Serology for Bartonella, Babesia, Anaplasma and Ehrlichia showed no indication of an active infection. Culture was negative for cryptococcosis, tuberculosis and other common bacteria. Results for Lyme disease showed specific intrathecal IgG antibodies against B. burgdorferi in ELISA, no additional bands on blot were seen in CSF compared to serum. The intrathecal antibody index (AI) was positive (AI 19; cut off 0.3), indicating a specific production of antibodies to Borrelia in the CSF (IDEIA, Oxiod, UK). Also real-time PCR for Borrelia burgdorferi OspA conducted on the CSF was positive . Serum antibodies against Borrelia were detected with the QuickELISA Borrelia C6 assay (Lyme index >10) (Immunetics, Boston, USA), and their presence was confirmed by a positive band for p100/83, VlsE, p41(i), p39 and DbpA on the RecomBlot Borrelia IgG assay (Mikrogen, Martinsreid, Germany). A serum from three years preceding this clinical presentation tested completely negative for antibodies against B. burgdorferi.
We describe a case of a patient with an HIV infection and severe neurology and MRI lesions due to a B. burgdorferi central nervous system (CNS) infection. After treatment with ceftriaxone the laboratory parameters of infection disappeared along with the abnormalities on MRI, however the patient persistently suffered from severe verifiable sequelae.
Diagnosing Lyme disease using serology in patients with HIV is complicated due to reduced positive predictive value of serology in HIV patients . Also, false positive serologic findings are described in patients with neurological infections with other spirochetes such as Treponema pallidum . Present patients' clinical presentation was compatible with a localised cerebral infection with B. burgdorferi, confirmed by the positive serology, intrathecal specific anti-Borrelia antibody production and a positive real-time PCR for B. burgdorferi OspA on the CSF. The sensitivity of the OspA real-time PCR on CSF is only about 50% but the specificity is very high >99% . In HIV positive patients where diagnosis of LNB by an indirect method such as serology is already compromised, a method where the microorganism is detected directly is of great value.
Little is known about the course of LNB in HIV patients. Animal models have shown that CD4 + T-cells facilitate clearance of B. burgdorferi . In recent studies the importance of CXCL13 in B-cell recruitment in patients with LNB has been suggested . In HIV infection the levels of CXCL13 in serum are elevated and the receptor CXCR5 on B-cells is down regulated causing impaired trafficking of B-cells . Inadequate humoral response could lead to accelerated progression of LNB. In animal experiments immunodeficiency leads to higher spirochete burdens and higher infectivity of B. burgdorferi . In contrast, reports from a study where Lyme borreliosis patients were treated with immunosuppressive agents, no significant effect on clinical course and response to treatment was observed . T. pallidum is a spirochete and more is known about disease course in syphilis HIV co-infection. Disease course is altered in T. pallidum and HIV co-infections; there is a higher rate of asymptomatic infection, a faster progression to secondary disease which is often more aggressive with a significant predisposition for the development of neurological complaints. However, after treatment HIV positive patients recover as well as the HIV negative population [13, 14]. In co-infections of HIV and Leptospira species. a more fulminant disease course has also been suggested . For LB and HIV co-infections no such synergistic complications have been described in patients to date.
Clinical data from all patients with LNB and HIV reported in literature.
Annular erythematous lesion
Several weeks later: fever, bilateral facial palsy
IV ceftriaxone 2 g/day 14 days
After treatment vast improvement 2 months, complete recovery
Headache, painful limbs, weight loss, pneumonia
Primairily: PO Azithromycin
Progression to neuroborreliosis
1 day 500 mg, 4 days 250 mg
2 weeks later: fever, diplopia
IV ceftriaxone 2 g/day 14 days
4 weeks later:: radiculitis
IV ceftriaxone 2 g/day 15 days
18 months, no relapse
Fever, chills, arthralgias
IV ceftotaxime 2 g TID 21 days
After treatment mild facial palsy
2 weeks later left facial palsy
6 months, slight hypokinesia face
Altered gait for months
IV ceftriaxone 2 g/day 1 month
After treatment severe sequelae
3 years, no relapse
Laboratory data from all patients with LNB and HIV reported in literature.
Blood CD4+ count (/μl)*
CSF cell count (/μl)
IgM +/IgG -
ELISA IgG + (month 4)
ELISA IgG + (month 4)
WB IgG +
WB IgG +
IF Negative >4 months
IgM +/IgG +
IgM +/IgG +
IgM -/IgG +
IgM -/IgG +
A clinician should consider LNB as a rare possible cause of focal encephalomyelitis in an HIV patient, without any history of Lyme disease or tick bites in an area endemic for Lyme disease. Diagnosis of LNB can be compromised in HIV co-infected patients, however when applying optimal serological and molecular diagnostic techniques confirming LNB is imminent. This report raises the possibility that LNB might take a more severe course in immunocompromised patients, such as those with HIV infection.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
The authors would like to thank Gerrit van der Luijt for preparing the CT and MRI pictures for publication and Pulak Goswami for proofreading the manuscript.
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